For the first time, a new study has shown it is possible to use low-power
lasers to spur stem cells in the body to make new tissue, in this case to regenerate dentin in
teeth. The Harvard-led team says their work lays the foundation for a wealth of new clinical
applications for healing wounds, regenerating bones and teeth, and more.

Senior author David J. Mooney, who is Robert P. Pinkas Family Professor of Bioengineering at
the Harvard School of Engineering and Applied Sciences, and colleagues report their study
in the journal Science Translational Medicine.

They describe not only how they used low-powered laser light to spur human dental stem cells to
form dentin - the bone-hard tissue that makes up the bulk of teeth - but also the precise
molecular mechanisms involved.

Currently, when using stem cells, scientists have to remove them from the body, work with them
in the lab, and then put them back in the body. Translating the results of research using this
approach to the clinic involves numerous hurdles - both regulatory and practical.

But the laser-based method the Harvard-led team is working on should be much easier to
translate to the clinic, as Prof. Mooney explains:

"Our treatment modality does not introduce anything new to the body, and lasers are routinely
used in medicine and dentistry, so the barriers to clinical translation are low. It
would be a substantial advance in the field if we can regenerate teeth rather than replace
them."

The work began when lead author and dentist Dr. Praveen Arany drilled holes in the molars of
laboratory rats. Dr. Arany treated the tooth pulp that contains adult stem cells with low-dose laser light,
sealed them with temporary caps and then just kept the animals comfortable and healthy and
waited.

Twelve weeks later, when he examined the results using high-resolution X-ray imaging and
microscopy, Dr. Arany, who is an Assistant Clinical Investigator at the National Institutes of
Health (NIH), found the laser treatment had triggered dentin formation.

Following this early success, the team took it to the next stage by performing a series of
experiments, using cultured tissue, to find out what happens at the molecular level when laser
light triggers new tissue formation.

Underlying molecular mechanism is a domino effect from laser trigger to dentin

They discovered that a common regulatory cell protein called transforming growth factor beta-1
(TGF-β1) plays a key role in triggering dental stem cells to grow into dentin.

The researchers now want to begin human trials for the laser treatment and are currently planning the required safety and efficacy tests.

Until a molecule comes along and activates it, TGF-β1 exists in a standby mode. What the team
discovered is a domino effect that begins when the laser light induces reactive oxygen species
(ROS), and these in turn activate the TGF-β1 complex, which then triggers the stem cells to
differentiate into dentin. ROS are chemically active oxygen-containing molecules that play a key
role in many cell functions.

The discovery is significant because it confirms scientifically what has always been believed
from reported anecdotes about low-level light therapy, also known as photobiomodulation. Since the 1960s, there have been anecdotal reports of doctors achieving remarkable results
with laser light such as rejuvenating skin, stimulating hair growth, and other wonders.

It is also interesting that the same type of laser therapy can be used to remove unwanted skin
material and hair - it all depends on how you use the laser.

The study helps to clarify some of the inconsistent evidence about the clinical effects of
low-power lasers on tissue, and marks the first time that scientists have come to grips with
the underlying molecular mechanisms involved.

Don Ingber, Founding Director of the Wyss Institute, that helped fund the study, says "the
scientific community is actively exploring a host of approaches to using stem cells for tissue
regeneration efforts," and with this new study, Prof. Mooney and his team have "added an
innovative, noninvasive and remarkably simple but powerful tool to the toolbox."

Dr. Arany now wants to begin human trials and is currently working with others to plan the
required safety and efficacy tests. He says they are also "excited about expanding these
observations to other regenerative applications with other types of stem cells."

As well as the Wyss Institute, the National Institute of Dental and Craniofacial Research of the NIH and various sources within Harvard, helped fund
the study.

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